A Study to Test the Addition of the Drug Cabozantinib to Chemotherapy in Patients With Newly Diagnosed Osteosarcoma

Recruiting now · Phase 2/Phase 3

Conditions studied: High Grade Osteosarcoma, Localized Osteosarcoma, Metastatic Osteosarcoma, Secondary Osteosarcoma

In brief

This phase II/III trial tests the safety, side effects, and best dose of the drug cabozantinib in combination with standard chemotherapy, and to compare the effect of adding cabozantinib to standard chemotherapy alone in treating patients with newly diagnosed osteosarcoma. Cabozantinib is in a class of medications called kinase inhibitors which block protein signals affecting new blood vessel formation and the ability to activate growth signaling pathways. This may help slow the growth of tumor cells. The drugs used in standard chemotherapy for this trial are methotrexate, doxorubicin, and cisplatin (MAP). Methotrexate stops cells from making DNA and may kill tumor cells. It is a type of antimetabolite. Doxorubicin is in a class of medications called anthracyclines. It works by slowing or stopping the growth of tumor cells in the body. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Adding cabozantinib to standard chemotherapy may work better in treating newly diagnosed osteosarcoma.

Key facts

Study ID

NCT05691478

Run by

National Cancer Institute (NCI)

People needed

1122

Starts

2023-03-03

Expected to finish

2030-03-20

Last updated by the study team

2026-07-31

Who can join

Age: any, up to 40. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must be < 40 years of age at the time of enrollment.
• Patients must have a body surface area of >= 0.8 m\^2 at the time of enrollment.
• Patients must have histologic diagnosis (by institutional pathologist) of newly diagnosed high grade osteosarcoma. Primary tumors of all extremity and axial sites are eligible as long as diagnosis of high-grade osteosarcoma is established. Osteosarcoma as a second malignancy is eligible if no prior exposure to systemic chemotherapies.
• Feasibility Phase (NOTE: as of Amendment #2B, the feasibility phase has been completed) Patients must have metastatic disease and a resectable primary tumor. Designation of a primary tumor as resectable will be determined at the time of diagnosis by the institutional multidisciplinary team.
• For this study, metastatic disease is defined as one or more of the following:
• Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor. Skip lesions in the same bone as the primary tumor do not constitute metastatic disease. Skip lesions in an adjacent bone are considered bone metastases.
• Lung metastases: defined as biopsy-proven metastasis or the presence of one or more pulmonary lesions >= 5 mm, OR multiple pulmonary lesions >= 3 mm or greater in size.
• Bone metastases: Areas suspicious for bone metastasis based on fludeoxyglucose F-18 (18F-FDG)-positron emission tomography (PET) scan (or whole body technetium-99 bone scan if 18F-FDG-PET is unavailable at the treating institution) require confirmatory biopsy or supportive anatomic imaging of at least one suspicious site with either magnetic resonance imaging (MRI) or computed tomography (CT) (whole body 18F-FDG-PET/CT or 18F-FDG-PET/MR scans are acceptable).
• Efficacy Phases (Phase 2/3) NOTE: as of Amendment #2B, the efficacy phase is open for enrollment.
• Patients with both localized and metastatic disease are eligible for the efficacy phase, regardless of resectability. Patients will be enrolled to two separate cohorts:
• Cohort 1 (Standard Risk): Patients with non-pelvic primary osteosarcoma deemed to be resectable at the time of diagnosis by the institutional multidisciplinary team, without evidence of metastatic lesions.
• Cohort 2 (High-Risk): Patients with a primary pelvic tumor, a primary tumor designated as unresectable by the institutional multidisciplinary team, AND/OR radiographic evidence of metastatic lesions.
• A serum creatinine based on age/sex as follows (within 7 days prior to enrollment unless otherwise indicated):
• (Age: Maximum Serum Creatinine [mg/dL]; Sex)
• 1 month to < 6 months: 0.4 (male); 0.4 (female)
• 6 months to < 1 year: 0.5 (male); 0.5 (female)
• 1 to < 2 years: 0.6 (male); 0.6 (female)
• 2 to < 6 years: 0.8 (male); 0.8 (female)
• 6 to < 10 years: 1 (male); 1 (female)
• 10 to < 13 years: 1.2 (male); 1.2 (female)
• 13 to < 16 years: 1.5 (male); 1.4 (female)
• >= 16 years: 1.7 (male); 1.4 (female)
• OR - a 24 hour urine creatinine clearance >= 70 mL/min/1.73 m\^2
• OR - a glomerular filtration rate (GFR) >= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).
• Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility.

You may not qualify if…

• Patients who have received previous systemic therapy for osteosarcoma or a prior oncologic diagnosis.
• Patients who have central nervous system metastases.
• Patients with central cavitating pulmonary lesions invading or encasing any major blood vessels in the lung.
• Patients who are unable to swallow tablets. Tablets cannot be crushed or chewed.
• Patients with gastrointestinal disorders including active disorders associated with a high risk of perforation or fistula formation. Specifically, no clinically significant gastrointestinal (GI) bleeding, GI perforation, bowel obstruction, intra-abdominal abscess or fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for 3 months prior to enrollment.
• Patients with active bleeding or bleeding diathesis. No clinically significant hematuria, hematemesis, or hemoptysis or other history of significant bleeding within 3 months prior to enrollment.
• Patients with uncompensated or symptomatic hypothyroidism. Patients who have hypothyroidism controlled with thyroid replacement hormone are eligible.
• Patients with moderate to severe hepatic impairment (Child-Pugh B or C).
• Patients who have had primary tumor resection or attempted curative resection of metastases prior to enrollment.
• Patients who have undergone other major surgical procedure (eg, laparotomy) within 14 days prior to enrollment. Thoracoscopic procedures for diagnostic purposes (biopsy of lung nodule) and central access such as port-a-cath placement are allowed.
• Patients with a history of serious or non-healing wound or bone fracture (pathologic fracture of primary tumor is not considered exclusion).
• Patients with any medical or surgical conditions that would interfere with gastrointestinal absorption of cabozantinib.
• Patients with previously identify allergy or hypersensitivity to components of the study treatment formulations.
• Patients who are receiving any other investigational agent not defined within this protocol are not eligible.
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
• Patients who received enzyme-inducing anticonvulsants within 14 days prior to enrollment.
• Patients with a prior history of hypertension (> 95th percentile for age, height, and sex for patients < 18 years and > 140/90 mmHg for patients >= 18 years requiring medication for blood pressure control.
• Patients who are receiving drugs that prolong QTc.
• Patients receiving anticoagulation with oral coumarin agents (eg warfarin), direct thrombin inhibitors (eg dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (eg, clopidogrel). Low dose aspirin for cardioprotection (per local applicable guidelines) and low dose, low molecular weight heparins (LMWH) are permitted. Anticoagulation with therapeutic doses of LMWH and direct factor Xa inhibitors rivaroxaban or apixaban are allowed in subjects who are on a stable dose for at least 6 weeks before the first dose of study treatment, and who have had no complications from a thromboembolic event or the anticoagulation regimen.
• Patients receiving strong CYP3A4 inducers or strong CYP3A4 inhibitors.
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
• Lactating females who plan to breastfeed their infants.
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of protocol therapy.

Where it is running

• Banner Children's at Desert — Mesa, Arizona, United States (enrolling)
• Phoenix Childrens Hospital — Phoenix, Arizona, United States (enrolling)
• Mayo Clinic Hospital in Arizona — Phoenix, Arizona, United States (enrolling)
• Banner University Medical Center - Tucson — Tucson, Arizona, United States (enrolling)
• Arkansas Children's Hospital — Little Rock, Arkansas, United States (enrolling)
• Kaiser Permanente Downey Medical Center — Downey, California, United States (enrolling)
• City of Hope Comprehensive Cancer Center — Duarte, California, United States (enrolling)
• Loma Linda University Medical Center — Loma Linda, California, United States (enrolling)
• Miller Children's and Women's Hospital Long Beach — Long Beach, California, United States (enrolling)
• Children's Hospital Los Angeles — Los Angeles, California, United States (enrolling)
• Cedars-Sinai Medical Center — Los Angeles, California, United States (enrolling)
• Mattel Children's Hospital UCLA — Los Angeles, California, United States (enrolling)
• Valley Children's Hospital — Madera, California, United States (enrolling)
• UCSF Benioff Children's Hospital Oakland — Oakland, California, United States (enrolling)
• Kaiser Permanente-Oakland — Oakland, California, United States (enrolling)
• Children's Hospital of Orange County — Orange, California, United States (enrolling)
• Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States (enrolling)
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States (enrolling)
• Rady Children's Hospital - San Diego — San Diego, California, United States (enrolling)
• UCSF Medical Center-Mission Bay — San Francisco, California, United States (enrolling)
• Children's Hospital Colorado — Aurora, Colorado, United States (enrolling)
• Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center — Denver, Colorado, United States (enrolling)
• Connecticut Children's Medical Center — Hartford, Connecticut, United States (enrolling)
• Yale University — New Haven, Connecticut, United States (enrolling)
• Children's Hospital of Alabama — Birmingham, Alabama, United States (enrolling)

Full record on ClinicalTrials.gov

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